The applicant, Teryl K. Frey, has been at his position as an Assistant Professor in the Biology Department at Georgia State University for almost six years. In that time, he has been able to develop in his laboratory a research program on the molecular biology of rubella virus. Rubella virus is a major human pathogen. Although controlled in the United States by a vaccination program, the virus is endemic in the rest of the world. Complication arising from rubella virus infection are birth defects and persistent infection. The vaccine strain virus has been shown to have the capacity of persisting. Persistent rubella virus infection has been associated with vaccine failure, some forms of chronic arthritis, and a rare, fatal neurodegenerative disorder. The molecular biology of rubella virus has only recently been elucidated in any detail. A major aim of the proposed research is to continue study of the molecular biology of this virus. A professional goal of the applicant is to apply the information elucidated from the study of the molecular biology of viruses to gaining understanding of viral pathogenesis in humans, particularly with regards to persistent infection, and to resolving some of the health problems caused by viruses. Therefore, the second major aim of the proposed research is to initiate studies directed toward the goal of approaching human health problems associated with rubella virus with molecular biological methods. An RCDA award is being applied for to allow the applicant the extra time needed to pursue this latter research aim which represents an amplification of the applicant's current research scope. The specific experimental initiatives to be undertaken in this effort are, first, to introduce the structural proteins of rubella virus into expression vectors with which candidate vaccines or diagnostic reagents can be designed. The second is to develop an assay with which to distinguish the wild type and vaccine viruses to determine if certain complications such as birth defects and chronic disease due to persistent rubella virus infection are caused by wild type infection, vaccination, or both. Thirdly, background studies will be done which eventually will lead to a study of rubella virus persistence in human. This involves developing vectors with which to study the cell mediated immune response to rubella virus and designing probes for the detection of persistent rubella virus infection in humans.